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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present paper reviews several studies performed between 1977 and 1986 in Singapore on the 10-year survival outcome of treatment for stage I and II hepatocellular carcinoma (HCC). Of 801 HCC patients evaluated, only 2 survivors (0.3%) remained in complete remission for 13 and 14 years, respectively. One had received four weekly cycles of prednisolone, Adriamycin, vincristine and 5-fluorouracil for an inoperable HCC with a 10-cm diameter, and the other had received localised synchronised hepatic irradiation and Adriamycin. As follow-up, the use of localised hepatic irradiation consisting of 131I-labeled (30 mCi) iodised oil in lipiodol infused via the hepatic artery appeared to benefit patients with small residual tumours but did not affect larger tumours measuring 2 cm in diameter. Prophylactic, intermittent long-term administration of lymphoblastoid interferon-alpha (Wellferon) was carried out in pre-cancerous, high-risk hepatitis B surface antigen (HBsAg)-positive patients with cirrhosis, in immediate male relatives of liver cancer patients, and in persons who had undergone hepatic resection. In the untreated group, 10/162 (6%) cirrhotics, 3/18 (17%) male family members, and 6/10 (60%) post-resection cases developed single or multiple HCCs within 1 year of screening done at 3-month intervals on the basis of alpha-fetoprotein (AFP) levels and real-time hepatic ultrasonography. In contrast, none of the Wellferon-treated group consisting of 518 cirrhotic patients, 82 male relatives of HCC patients and 20 post-resection cases developed HCC. Two HBsAg-positive individuals who had not been treated with interferon (IFN) developed hepatic nodules which that showed dysplasia, AFP elevation and chromosomal changes. These studies demonstrate the poor results of late diagnosis and show that early intervention and prophylaxis with Wellferon can reduce the incidence of HCC in high-risk persons. In addition, transhepatic chemoembolisation and liver resection are suitable methods for treating small HCCs (single or multiple) that are detected by screening. However, some of these early-detected HCCs remain highly malignant. Prophylactic treatment of pre-cancerous conditions appears to be a better option as a long-term programme for HCC.
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PMID:Long-term survival following treatment of hepatocellular carcinoma in Singapore: evaluation of Wellferon in the prophylaxis of high-risk pre-cancerous conditions. 133

The effect of interferon-alpha 2b (IFN) on viral markers, liver function and immunological parameters (CD3, CD4, CD8, B, NK, II-2 receptor and HLA-DR positive cells in blood and T cell proliferation) was studied in 9 patients with HBsAg(+), HBeAg(-) chronic active hepatitis (CAH). Three patients were HBV-DNA(+) and 6 also had complications of cirrhosis of the liver (LC). IFN was given at a dose of 2.5 mil IU x 3 weekly for 6 months. One patient with LC developed hepatic coma and died 2 months later. Severe leukopenia limited duration of treatment to 2 and 4 months in another 2 patients. By the end of treatment, the 8 patients were in good clinical status, SGOT, SGPT levels and prothrombin time were decreased, HBV-DNA became negative in 2 out of 3 patients and proportions of CD3, CD4, B, NK and activated cells were significantly decreased. When compared to controls, NK and activated cells were significantly increased in patients before and were gradually decreased by the end of treatment. In contrast, T transformed cells were significantly decreased before and ranged in normal levels by the end of treatment. These findings suggest that immunomodulatory activity possibly contributes to the beneficial effect of IFN therapy.
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PMID:alpha-Interferon therapy in patients with chronic active hepatitis B: immunological profile. 166 91

The interferons (IFN) act too slowly to arrest acute viral infections, but interferon-alpha (IFN alpha) preparations have proved useful in some chronic infections and will clearly be used increasingly in these in the future. In the preparations derived from human leucocytes or cultured B lymphoblastoid cells, which are in routine clinical use, mixtures of a number of distinct subtypes of human IFN alpha have been identified. There are also 3 slightly different versions of the same single subtype, IFN alpha-2, made by recombinant DNA procedures in bacteria. IFN alpha preparations are injected intramuscularly or subcutaneously. Dose-related side effects are common but usually tolerable, but prolonged treatment may cause increasing fatigue and depression. Some patients form neutralising antibodies which block the effects of the IFN; these appear to be relatively more common after recombinant IFN alpha-2 than after IFN derived from human cells. Given intranasally, IFN alpha can prevent a subsequent experimental rhinovirus infection, or the spread of natural colds within a family. Repeated administration progressively damages the nasal mucosa, so that long term prophylaxis is not possible. IFN alpha has proved useful in patients with papillomavirus warts of the larynx, ano-genital region (condyloma acuminata) and skin (common warts). Treatment regimens remain to be optimised and are likely to include surgery or other treatments. IFN alpha and zidovudine (azidothymidine) synergistically inhibit the growth of HIV in vitro, and combination are on trial in patients with early AIDS. Very large doses of IFN alpha are effective against Kaposi's sarcoma in some AIDS patients. In chronic hepatitis B, continuing virus replication may lead to cirrhosis or primary liver cancer. Earlier clinical trials with IFN alpha gave inconclusive results, but recent large studies have confirmed that 25 to 40% of patients obtain benefit; this probably results from both the antiviral and the immunomodulatory effects of IFN alpha. In patients with chronic hepatitis C, the biochemical markers usually improve rapidly during IFN alpha administration, but relapse if treatment is stopped after only a few months; to increase the chances of sustained cure, the treatment period is now being prolonged.
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PMID:The use of interferon-alpha in virus infections. 172 72

Reinfection of the graft with hepatitis B virus (HBV) and hepatitis delta virus (HDV) is a potential complication in patients undergoing orthotopic liver transplantation (OLT). Therefore, we added recombinant interferon-alpha (rIFNa) to the standard immunosuppressive regimen in 11 patients who received transplants following liver failure attributed to cirrhosis B (n = 10, with HDV co-infection in four cases) or fulminant hepatitis B (n = 1). Patients were treated with rIFNa for periods ranging from 2 to 3 months between the first and the 13th month after OLT. All patients received immunosuppressive treatment with low-dose corticosteroids, azathioprine and cyclosporine. Anti-HBs hyperimmune globulin was also administered. None of the patients showed evidence of severe allograft rejection. Seven patients suffered HBV reinfection of the graft with histological signs of acute hepatitis in five cases and transition to chronic hepatitis in one patient. Treatment with rIFNa did not prevent or reduce HBV replication. Reinfection of the graft with HDV was demonstrated by PCR in four patients co-infected with HDV. During treatment with rIFNa liver biopsy specimens from three reinfected patients were transiently negative for HDV antigen but not for HDV RNA, and the sera from two patients were transiently negative for HDV RNA. The data indicate that rIFNa can reduce HDV replication in reinfected liver allografts.
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PMID:Follow-up of recurrent hepatitis B and delta infection in liver allograft recipients after treatment with recombinant interferon-alpha. 180 26

In a 59-year-old patient presenting in October 1981 with pancytopenia, hairy cell leukemia was diagnosed. Splenectomy, followed by treatments with oncovin, lithium, and prednisone were essentially without effect. Up to July 1984 the patient had been regularly transfused with a total of 62 unit. In June 1984 he acquired a transfusion associated hepatitis C which followed a chronic course and resulted in biopsy proven cirrhosis in 1989. The patient became independent of transfusions in July 1984. Repeated blood counts have shown a complete hematologic remission which has now lasted nearly 6 years, whereas focal leukemic infiltrates have persisted in the bone marrow. The patient has tolerated 20 courses of erythropheresis performed because of biopsy proven severe hepatic siderosis without a fall in hemoglobin. It is suggested that the spontaneous long-lasting hematologic remission of hairy cell leukemia is due to endogenous interferon produced in the course of chronic hepatitis C. Low serum levels of interferon-alpha and -gamma were detected.
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PMID:[Peripheral spontaneous remission of hairy cell leukemia following transfusion-associated hepatitis C]. 190 85

The study of chronic liver disease has been hampered by insufficient information relative to the pathogenesis of the many forms of hepatitis. Consequently, well-designed treatment strategies are frequently lacking. Wilson's disease is characterised by excessive copper accumulation in the liver and other organs. While d-penicillamine is clearly effective, many patients may not tolerate its many adverse effects. Trientine, oral zinc and unithiol have all shown promise as therapeutic alternatives. Autoimmune chronic active hepatitis responds well to prednisone and azathioprine. Cyclosporin has also produced clinical improvement in several case reports but no comparison has yet been made with the current standard therapy. Recombinant interferon-alpha (IFN alpha) has demonstrated the ability to inhibit hepatitis B viral replication, and the combination of oral corticosteroids followed by IFN alpha is more effective than either agent alone in eliminating viral replication in patients with chronic active hepatitis B. Currently, primary sclerosing cholangitis (PSC) has no standard medical management, but corticosteroids and methotrexate may each have a future role in its treatment. Drug treatment for primary biliary cirrhosis (PBC) has been disappointing, and early reports of success with d-penicillamine were not confirmed in large well-controlled trials. While some reports of improvement with several agents have been described, larger studies are still needed. Alcoholic liver disease continues to be associated with significant morbidity and mortality and numerous investigators have researched several different medical avenues of treatment. Success reported with androgens and the antithyroid agent propylthiouracil in alcoholic liver disease will need confirmation by other research before these agents can be recommended for routine use. Finally, colchicine may prove to be effective in slowing the rate of fibrosis in cirrhosis, but this has yet to be conclusively proven.
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PMID:Current therapy of chronic liver disease. 219 64

The occurrence of antibodies to interferon-alpha 2a (anti-IFN-alpha 2a) to recombinant human IFN-alpha 2a was examined in chronic liver disease by a sensitive enzyme-linked immunosorbent assay (ELISA). Naturally occurring IgG and/or IgM anti-IFN-alpha 2a were found in one of 12 cases of chronic persistent hepatitis, four of 18 cases of chronic active hepatitis (CAH), two of 12 cases of liver cirrhosis, six of seven cases of primary biliary cirrhosis, nine of 11 cases of auto-immune CAH and none of 21 normal control subjects. Fifteen patients with viral CAH were treated with recombinant IFN-alpha 2a. Two of them were positive prior to receipt of IFN-alpha 2a and their titres increased after the therapy. Two patients became positive for anti-IFN-alpha 2a after the therapy. Absorption experiments revealed that anti-IFN-alpha 2a cross-reacted with native human leucocyte IFN-alpha and recombinant IFN-alpha 2b but not with recombinant IFN-beta and -gamma. The immunoblotting experiment confirmed the binding of antibodies to IFN. The results of anti-IFN-alpha 2a obtained by antiviral, cytopathic effect assay were in good agreement with those of IgG anti-IFN-alpha 2a, but not with those of IgM antibodies obtained by the ELISA. The ELISA described in the present study is a simple, sensitive and quantitative assay for anti-IFN-alpha 2a. It should be useful in assessing sub-specificities of anti-IFN and provide valuable information to predict the effect of IFN therapy and to elucidate the immunological abnormality in liver disease.
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PMID:Detection of anti-interferon-alpha 2a antibodies in chronic liver disease. 249 Dec 7

The natural killer (NK) cell activity of peripheral blood lymphocytes (PBL) in patients with various chronic liver diseases, and its in vitro response to human interferon-alpha(Le) were investigated using a 16-h 51-Cr releasing cytotoxicity assay against YAC-1 or RSa target cells. The NK cell activity was found to be higher in chronic active hepatitis (CAH) and liver cirrhosis (LC) patients without HCC, whereas it was slightly lower in LC patients with hepatocellular carcinoma (HCC), than in normal controls. By the addition of IFN-alpha(Le) in vitro, the NK cell activity was clearly and dose-dependently augmented, even in chronic liver diseases, as well as in normal controls. The magnitude of this augmentation by 10,000 IU/ml of IFN-alpha(Le) in the various chronic liver diseases was not significantly different from that in normal controls. The results suggested that the response of NK cells to IFN-alpha(Le) is not impaired even in chronic liver disease conditions, while the level of NK cell activity may vary according to the type of chronic liver disease and may decrease in patients with HCC.
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PMID:Natural killer (NK) cell activity and its in vitro response to interferon-alpha(Le) in chronic liver diseases and hepatocellular carcinoma. 302 99

For patients with chronic hepatitis B e (HBe)-positive hepatitis, long-term results of pilot studies with lymphoblastoid interferon-alpha, acyclovir, or a combination, and of a randomized controlled trial of interferon/desciclovir combination therapy are presented. HBe seroconversion was observed in more than 40 percent of patients treated with combination therapy, 30 percent with interferon therapy, 18 percent with acyclovir, and 0 percent with no treatment. HBe reactivation occurred in two patients with cirrhosis. Hepatitis B surface seroconversion followed HBe seroconversion in 11 to 30 percent of treated patients. HBe seroconversion was significantly related to initial low levels of viral replication and to transient aminotransferase elevation during the second half of the interferon treatment of 16 weeks. Clinical improvement and persistent normalization of aspartate aminotransferase was observed in all patients with HBe seroconversion. Conversion to a state of virus latency (HBe negative) mostly occurred after therapy, suggesting that the specific immunologic host response had been brought about by the suppression of virus replication through antiviral agents. Recommendations for selection of patients for antiviral combination therapy are made on the basis of these long-term results.
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PMID:Long-term follow-up of antiviral combination therapy in chronic hepatitis B. 304 80

A monoclonal antibody to human interferon-alpha (IFN-alpha) was produced using affinity-purified IFN-alpha, that reacted with recombinant human IFN-alpha 2, but not with IFN-alpha 1, IFN-alpha M1 or IFN-beta. Indirect immunofluorescence using this monoclonal (designated 6C3) and anti-IFN-alpha polyclonal antibodies identified cells expressing IFN-alpha. After Sendai virus induction of normal human buffy-coat cells the proportion of monocytes and lymphocytes expressing IFN-alpha rose progressively from 0% to 50% and 34% respectively, preceding peak IFN-alpha titres in the culture supernatants. Around 80-90% of polymorphs were IFN-alpha-positive using both antisera, with or without IFN induction, although very little IFN bioactivity was released to the supernatant of polymorph cultures after IFN induction. Sections of hepatitis B virus infected human liver tissue showed foci of IFN-alpha-positive infiltrating mononuclear cells and (to a lesser extent) fibroblasts in patients who had active cirrhosis and evidence of virus replication. These findings suggest that polymorphs constitutively express IFN-alpha 2 related antigenic activity, whose biological activity is at present unknown; and demonstrates the identification of IFN-alpha-expressing cells in sections of tissue undergoing natural virus infection.
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PMID:Production of a monoclonal antibody to human interferon-alpha (IFN-alpha) and its use to identify IFN-alpha-producing cells in virus infection in vivo. 350 87


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